This proposal is concerned with the mechanical and electrical properties of cells in the organ of Corti and how those properties influence the ability of the organ to process sounds. In particular, the experiments are designed to determine how the outer hair cells (OHCs) function in vivo to control the vibration of the basilar membrane and cellular structure of the organ. It is thought that OHCs use their inherent motile ability to amplify sound-evoked vibration of the neurosensory structures in the cochlea. This process is called cochlear amplification. However, it is not known how OHCs accomplish this amplification, a property critical to normal hearing because it provides both for the great sensitivity of the ear and for the acuity needed to understand speech in a noisy environment. The amplifier mechanism must work within a system of mechanical and electrical filters. In Aim 1 we test the hypothesis that the stereocillia of OHCs act as a critical mechanical filter that has not yet been studied. The amplifier must also generate power and it is clear OHCs have cellular or subcellular motor activity that may provide the power. In Aim 2 we will determine whether cochlear amplification requires forces produced by the stereocilia (via so called fast adaptation) of OHCs or prestin motor molecules in the baso-lateral membrane of the OHC or both. The manipulation of endolymphatic calcium is key to the Aim 1 and 2 experiments. Finally, cochlear amplification can only come about with the proper (but as yet unknown) micromechanical motions of the system of cells that make up the organ of Corti. In Aim 3 we study the micro or cellular mechanics of the organ of Corti (in yivo) using custom designed measurement instrumentation based on low coherence optical interferometry. We investigate the mechanical processing of sound that occurs with activity of the OHCs and the resulting stimulation of the stereocilia of inner hair cells. Knowledge of OHCs and organ of Corti mechanics is essential to our understanding of the normal and pathophysiologial function of the cochlea. Data derived in these studies are critically needed for appropriate mathematical modeling of the inner ear and in turn such models provide the only way to completely understand its complex mechanics. [unreadable] [unreadable] [unreadable]